Nanoengineering of cyclic dinucleotide-manganese complexes using biodegradable mesoporous silica nanoparticles for cancer metallo-immunotherapy
발표자
Isra Rana (Chonnam National University)
연구책임자
남주택 (Chonnam National University)
공동저자
Isra Rana (Chonnam National University), 남주택 (Chonnam National University)
초록
내용
STING activation via cyclic dinucleotides is a promising cancer immunotherapy approach, investigated clinically. However, minimal cellular permeability, limited tumor distribution, and potential off target toxicities hinder its widespread applications. Herein, biodegradable mesoporous silica nanoparticles (bMSNs) were used to accommodate and stabilize the coordination polymer of cyclic di-AMP (CDA) and manganese ion for their efficient delivery and synergistic STING activation. CDA-Mn@bMSNs promoted cellular uptake and cytosolic delivery of CDA, leading to strong activation and maturation of BMDCs together with the co-delivered Mn2+. They also induced immunogenic cell death and apoptosis of cancer cells with the generation of reactive oxygen species. CDA-Mn@bMSNs improved antitumor immune responses and antitumor efficacy of CDN after intratumoral administration in murine melanoma models, which could be further augmented using immune checkpoint inhibitors.